Cost-Utility of Anti-VEGF Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion

Abstract

Objective:

To evaluate the cost-utility of treatment for macular edema in central retinal vein occlusion (CRVO) using intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents bevacizumab, ranibizumab, and aflibercept.

Design:

A decision analysis model of cost-utility.

Participants:

Data from study participants in the Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO) study.

Methods:

A decision analysis of a disease simulation model was used to calculate comparative cost-utility of intravitreal bevacizumab (IVB), ranibizumab (IVR), and aflibercept (IVA) for the treatment of macular edema associated with CRVO based on data from LEAVO study. Center for Medicare and Medicaid Services data were used to calculate associated modeled costs in a hospital/facility based and non-facility setting from a third-party payer perspective, and societal costs were also calculated. Cost-utility was calculated based on the preserved visual utility during the 2 years of the study and also by estimating utility for the expected lifetime.

Main Outcome Measures:

Cost of treatment, cost/QALY, incremental cost-effectiveness ratio (ICER)

Results:

From the third-party payer perspective, the estimated life-time cost/QALY in the facility (non-facility) setting was $39,325 ($17,944) for IVB, $114,095 ($92,653) for IVR, and $78,935 ($63,270) for IVA. From the societal perspective the estimated life-time cost/QALY in the facility setting was $52,754 for IVB, $128,242 for IVR, and $86,262 for IVA. The incremental cost-effectiveness ratio (ICER) of IVA compared to IVB was $153,633/QALY from the third-party facility setting and ($152,992/QALY) from the societal perspective. The use of IVB compared to IVR and IVA compared to IVR were cost-saving interventions (ICER<0) irrespective of the perspective or setting.

Conclusions:

In the treatment of macular edema in CRVO, IVB yields the best cost-utility among the three anti-VEGF agents modeled. IVA maintains acceptable lifetime cost/QALY, while having a favorable cost-utility compared to IVR.

Precis:

In the treatment of macular edema related to central retinal vein occlusion, intravitreal bevacizumab has the best cost-utility of all anti-VEGF agents. Intravitreal aflibercept also has acceptable cost-utility and is favorable compared to intravitreal ranibizumab.

INTRODUCTION

It is estimated that 0.08% of the population is affected by central vein occlusion (CRVO).^1,2 Macular edema is the most prevalent cause of visual impairment in patients with CRVO.^3,4 Vascular endothelial growth factor (VEGF) stimulates angiogenesis and vascular leakage, leading to macular edema.⁵ Macular edema is treated with intravitreal injections of licensed anti-vascular endothelial growth factor (anti-VEGF) agents ranibizumab (IVR) (Lucentis; Genentech Inc., South San Francisco, CA) and aflibercept (IVA) (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, NY).^6–10 Intravitreal bevacizumab (IVB) has also been reported to be effective, showing non-inferiority compared to aflibercept.¹¹ Intravitreal corticosteroid treatment has also been reported to be beneficial.^12–14

The Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO) trial compared the clinical effectiveness of the three anti-VEGF agents in treating macular edema related to CRVO.¹⁵ This trial showed that IVA was noninferior compared to IVR, whereas IVB was not noninferior to IVR at 100 weeks, in terms of visual acuity gains. While IVB has generally been regarded as a low-cost option in the treatment of other retinal vascular disease such as proliferative diabetic retinopathy and diabetic macular edema, cost-utility comparisons analyzing anti-VEGF treatment for macular edema have been mostly among diabetes, rather than related to CRVO.^16–20 This study aims to determine the cost-utility considerations of the three anti-VEGF agents for treatment of this disease.

METHODS

A cost-effectiveness analysis using a disease simulation model was based on published use and outcomes data from the Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO) study, a randomized, prospective clinical trial comparing IVB, IVR, and IVA as the primary treatment for macular edema in central retinal vein occlusion.¹⁵ Institutional review board approval was not required since there were no research participants or medical records reviewed.

Medicare fee data from the 2020 Centers for Medicare and Medicaid Services schedules were used to calculate the allowable cost (in 2020 US dollars) associated with each injection, study, or office visit.^21–23 Costs were calculated for both a hospital-based facility and a non-facility setting to frame the full range of practice setting costs. The dollars conversion factor per relative value unit (RVU) for 2020 was $36.0896.²¹ The equation used to calculate the cost for a given provider service included work RVUs in the form of professional fees, practice expense RVUs, and malpractice RVUs. Each of these factors was subject to geographic modifiers. For this analysis, the rates for Miami, Florida were used.

The costs were separated according to societal and third-party payer perspectives. Societal costs included all costs incurred, including formal medical costs (ie. Service fees), informal medical costs (ie. Transportation costs), and non-healthcare sector costs (ie. Productivity loss). The third-party payer perspective included only certain direct medical costs such as physician services, medications, anesthesia fees, and facility fees.^24,25 All societal values (employment, mean wages, etc) were taken from the 2019 data, but adjusted to 2020 US dollars.

The CPT codes used for intravitreal injection was 67028 (Table 1). Imaging codes for optical coherence tomography was CPT 92134. A comprehensive eye code (CPT 92004) was included for the initial visit, with subsequent follow-up visits calculated using the intermediate eye code (CPT 92012). The Healthcare Common Procedure Coding System code used for bevacizumab was J9035, for ranibizumab was J2778, and for aflibercept was J0178. The reimbursement schedules for procedures were based on the Centers for Medicare and Medicaid Services terminology for procedures performed in the facility and non-facility settings. In the case of endophthalmitis, a previously published facility cost for healthcare and societal setting was taken from the literature and adjusted to 2020 US dollars.²⁶

Table 1.

Medicare Allowable Costs For Intravitreal Bevacizumab, Ranibizumab, and Aflibercept, Along With Associated Treatments

Procedure	Facility					Non-Facility
	CPT Code	Professional Fee	Facility Fee	Anesthesia	Total	Professional Fee	Facility Fee	Anesthesia	Total
Intravitreal injection	67028	$108	$310	$0	$418	$110	$0	$0	$110
Bevacizumab	J9035 (HCPCS code)	$50 (Stocking Fee $2)
Ranibizumab	J2778 (HCPCS code)	$1717 (Stocking Fee $74)
Aflibercept	J0178 (HCPCS code)	$1877 (Stocking Fee $81)
OCT	92134	$44	$55	$0	$99	$44	$0	$0	$44
New Comprehensive Eye Exam	92004	$103	$116	$0	$219	$157	$0	$0	$157
Intermediate Follow Up Exam	92012	$71	$116	$0	$187	$125	$0	$0	$125

CPT= current procedural terminology; HCPCS= Healthcare Common Procedure Coding System; IVB= intravitreal injection bevacizumab; IVR= intravitreal injection ranibizumab; IVA= intravitreal injection aflibercept; OCT= optical coherence tomography;

^*Values calculated reflect geographic modifier Miami, Florida

Reimbursement for bevacizumab was estimated to be $50 per 1.25 mg injection, although the actual rate in most settings is likely to be lower. The Food and Drug Administration-approved IVR dose of 0.5 mg was used in this cost-analysis. According to the 2020 Centers for Medicare and Medicaid Services reimbursement rates, reimbursement per 0.1 mg unit of IVR is $343.309, and reimbursement per 1 mg unit of IVA is $938.443.²³ A drug maintenance fee of 4.3% of the medication costs was applied to the overall injection cost in each group. As used in this study, a dose of ranibizumab 0.5 mg cost $1717 and the 4.3% drug maintenance fee was $74, while a dose of aflibercept 2 mg was $1877 and the 4.3% drug maintenance fee was $81. In the facility setting the cost model included both the professional and facility charges, whereas in the non-facility setting there are no facility charges for injections. No anesthesia professional fees were applicable as it was assumed that all injections were done in the office.

As previously described and reported, a similar decision analysis Markov model, using within-cycle correction, was formulated to generate a total cost and cost per quality-adjusted life year (QALY) for each treatment scenario based on assumptions from the LEAVO trial.^16,18 The analysis incorporated the costs (and utilities) over 100 weeks and estimated to lifetime assuming maintenance of same utility; life expectancy years were obtained from the actuarial tables of the Social Security Administration (weighted by gender).²⁷

The utility gained by visual improvement to 20/50 from a baseline of 20/80 (conversion of Early Treatment Diabetic Retinopathy Study letter score to Snellen visual acuity) using IVB or IVR is 0.77 – 0.71= 0.06 utility units.²⁸ For IVA, the improvement was from 20/80 to 20/40, with utility being 0.8 – 0.71= 0.09 utility units. In all cases, the best corrected visual acuity (BCVA) in the treated eye was assumed to be equal to or worse than that in the fellow eye, so that the visual acuity-based utility values of the better-seeing eye were used. Similar cost-analysis calculations (although based on less extensive data) were made for the use of anti-VEGF agents in CRVO as reported in the CRUISE, COPERNICUS, and SCORE2 studies.^6,10,29,30 Additionally, the incremental cost-effectiveness ratio (ICER) was calculated for treatment eyes by dividing the incremental cost of IVA compared to IVB and IVR, as well as IVR compared to IVB, by the incremental utility gained according to the improvement in visual acuity score.

The LEAVO study did not report data beyond 100 weeks. Hence, calculations to model lifetime usage and utility were estimated based on reasonable clinical judgement. The frequency of injections for subsequent years after 100 weeks was modeled as 2 per year for the remaining life years in all injection groups, but were varied from 1 to 4 for the sensitivity analysis. An assumption of 4 follow up visits per year in all injection groups was made. It was assumed that this regimen yielded maintenance of the BCVA. Endophthalmitis rates were varied between 0.02% and 0.1%. All future costs and utilities were discounted in a standard 3% inflation rate per year.

One-way deterministic sensitivity analyses and probabilistic sensitivity analyses (PSA) using second-order Monte Carlo simulations repeated 100,000 times to assess for uncertainty were performed. The least to most expensive clinical scenarios were used to determine the ranges of the PSA. Parameter uncertainty was assessed by varying the number of anti-VEGF injections, and the utility of each therapy; structural uncertainty was assessed by incorporating and varying the incidence of endophthalmitis. Calculations and analyses were performed using TreeAge Pro Healthcare Version 2020 (TreeAge Software LLC. Williamstown, Massachusetts).

RESULTS

The unit costs, including the facility and professional fees (Table 1) were applied to the estimated frequency of resource use based on the average number of treatments over 100 weeks in all injection groups (Table 2). These results yielded cost-utility measures for third party and societal perspectives (Table S1–2). The proportional costs of professional fees, imaging, and drug costs for treatment were calculated (Figure 1). According to trial period length, cost/QALY data as extrapolated from CRUISE, SCORE2, and COPERNICUS trials are shown in Table 3.

Table 2.

Estimated Use of Resources Based on Injection Over 100 Weeks (based on LEAVO trial data¹)

Procedure	CPT code	Scenario 1, IVB	Scenario 2, IVR	Scenario 3, IVA
New Comprehensive Eye Exam	92004	1	1	1
Intermediate Follow Up Exam	92012	24	24	24
Intravitreal injection	67028	11.5	11.8	10
OCT	92134	24	24	24

CPT= Current procedural terminology; IVB= Intravitreal bevacizumab; IVR= Intravitreal ranibizumab; IVA= Intravitreal aflibercept; OCT= optical coherence tomography

¹Hykin P, Prevost AT, Vasconcelos JC, et al. Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion: A Randomized Clinical Trial. JAMA Ophthalmol 2019.

Figure 1.

Proportional costs of professional fees, imaging, and drug costs for treatment over 100 weeks of treatment. IVB= intravitreal bevacizumab; IVR= intravitreal ranibizumab; IVA= intravitreal aflibercept

Table 3.

Cost/QALY from a Third Party Payer Perspective Extrapolated From LEAVO¹, CRUISE², SCORE2³, and COPERNICUS⁴ Trials According to Trial Length

		LEAVO- 100 weeks	CRUISE- 6 months	SCORE2- 24 months	COPERNICUS- 2 years
Cost/QALY- Facility (Non-Facility)	IVB	$97,804 ($46,343)		$155,668 ($71066)
	IVR	$270,666 ($218,808)	$75,267 ($62260)
	IVA	$166,901 ($135,509)		$430,154 ($350470)	$363,642 ($292565)

IVB= Intravitreal bevacizumab; IVR= Intravitreal ranibizumab; IVA= Intravitreal aflibercept; QALY= quality adjusted life years

¹Hykin P, Prevost AT, Vasconcelos JC, et al. Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion: A Randomized Clinical Trial. JAMA Ophthalmol 2019.

²Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 2010;117(6):1124–33 e1.

³Scott IU, Oden NL, VanVeldhuisen PC, et al. Month 24 Outcomes After Treatment Initiation With Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Due to Central Retinal or Hemiretinal Vein Occlusion: SCORE2 Report 10: A Secondary Analysis of the SCORE2 Randomized Clinical Trial. JAMA Ophthalmol 2019.

⁴Heier JS, Clark WL, Boyer DS, et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology 2014;121(7):1414–20 e1.

Group 1: Bevacizumab (IVB)

The 100-week third-party cost for facility (non-facility) treatment was $12,085 ($5,867), with a cost/QALY of $97,804 ($46,343) for the first 100 weeks of utility. The modeled lifetime cost was $34,504 ($16,751) (Figure 2), while the lifetime cost/QALY was estimated as $39,325 ($17,944).

Figure 2.

Estimated cumulative lifetime cost of additional therapy from societal and third party perspective. IVB= intravitreal bevacizumab; IVR= intravitreal ranibizumab; IVA= intravitreal aflibercept

Varying the endophthalmitis risk had a very small impact on the overall costs and effectivity. Varying the number of maintenance injections after the initial 100-week period had a considerable impact on the lifetime cost/QALY with ranges from $32,791–52,655 ($15,628–22,479).

Group 2: Ranibizumab (IVR)

The third-party cost of treatment with IVR for 100-weeks was $32,160 ($25,896), with cost/QALY $270,666 ($218,808) for that time period. The modeled lifetime cost was $91,031 ($73,235), while the lifetime cost/QALY was estimated as $114,095 ($92,653) (Figure 2). The CRUISE trial established the clinical efficacy of IVR, and over the trial’s 6-month period the cost/QALY of IVR (0.5 mg) was $75267 ($62260).

Varying the endophthalmitis risk had a very small impact on the overall costs and effectivity. Varying the number of maintenance injections after the initial 100-week period had a considerable impact on the lifetime cost/QALY with ranges from $83,770–177,074 ($66,546–146,837).

Group 3: Aflibercept (IVA)

For IVA, the 100-week third-party cost was $29,810 ($24,098), with cost/QALY $166,901 ($135,509) during this time. The modeled lifetime cost was $94,295 ($74,944), and estimated lifetime cost/QALY was $78,935 ($63,270) (Figure 2). Varying the endophthalmitis risk had a very small impact on the overall costs and effectivity. Varying the number of maintenance injections after the initial 100-week period had a considerable impact on the lifetime cost/QALY with ranges from $55,300–122,185 ($44,313–102,526).

The COPERNICUS trial demonstrated the clinical efficacy of IVA, and using the 2-year results showed a cost/QALY of $363642 ($292565), with a lifetime cost/QALY (assuming ongoing treatment burden mirrored that of the LEAVO data) of $89140 ($71605). When using 24 month SCORE2 trial results comparing IVB to IVA, the 24 month cost/QALY would be $155668 ($71066) for IVB and $430154 ($350470) for IVA. Estimated lifetime cost/QALY of IVB would be $31389 ($16114) whereas the lifetime cost/QALY of IVA would be $94278 ($76000).

Interdrug Comparison

The ICER of IVA compared to IVB over 100 weeks in a facility (non-facility) setting was $304,955/QALY ($313,659/QALY); there was very little variance by adjusting the incidence of endophthalmitis. With lifetime costs, the facility cost/QALY changed to $153,633, with a range of $100,125 to $260,649 by varying the maintanence yearly injection rate from one to four.

Since both IVB and IVA had both a lower cost and better utility compared to IVR, these yielded a negative ICER, and are thus considered to be cost-saving interventions when compared to IVR in every scenario and perspective studied.

Sensitivity Analysis

An average of 13.4 (32) injections in the facility (non-facility setting) per year would be needed for the lifetime cost/QALY of the IVB group to equilibrate with the IVR group (assuming this last group was stable at a 2 per year maintenance rate). On average 3.8 (3.5) injections per year would be needed for the lifetime cost/QALY of the IVA group to equilibrate with the IVR group (Figure 3).

Figure 3.

Sensitivity Analysis: Lifetime Cost/QALY With Various Rates of Annual Injections Beyond Week 100 (Societal). IVB= intravitreal bevacizumab; IVR= intravitreal ranibizumab; IVA= intravitreal aflibercept

If instead of assuming all treated eyes are the better seeing eye, we assume this is the case only 44% of the time, the estimated lifetime cost/QALY would be 2.28 times higher for all agents.³¹

DISCUSSION

The cost-utility of anti-VEGF agents for the treatment of macular edema related to CRVO was calculated and compared based on the LEAVO 100 week data.¹⁵ There was a higher cost/QALY of IVR compared to both IVB and IVA—IVR was 2.8 to 4.7 times that of IVB, and 1.6 times that of IVA. Lifetime cost/QALY of IVR was 2.9 to 5.2 times that of IVB, and 1.4 to 1.5 times that of IVA. If only considering the cost-utility for 100 weeks under study, from a societal perspective all agents were above the generally acceptable range of $50000 to $100000/QALY (“willingness to pay”).²⁸ However, assuming stable visual acuity and average lifetime expectancy, both IVB and IVA fall within the acceptable range of cost/QALY, while IVR still exceeded it. The cost-utility of anti-VEGF agents in the treatment of vein occlusions is likely to be affected by not only the specificity of the condition but also by differential costs of treatment in various healthcare settings. A study from the U.K. demonstrated improved lifetime cost-utility of IVR over IVA for treatment of macular edema in branch vein occlusions, which would be difficult to extrapolate to treatment for CRVO in the U.S.³² The differences in healthcare economics, namely the pricing of medication and willingness to pay threshold, prevent adequate comparison.

The ICER calculations are perhaps more valuable to compare the cost-utility differences, given that some treatment is the standard of care, and they show much higher costs for IVA and especially IVR regardless of practice setting and treatment duration modeled.³³ When compared to IVB, IVA has a high ICER value despite its acceptable cost-utility profile, indicating a very high marginal cost relative to the marginal benefit in vision/utility. IVR has an even higher greater ICER compared to IVB, while IVA maintained superior cost-utility over IVR. The drug cost of IVB makes up a small percentage of the total costs of treatment; in contrast, the drug cost of IVR and IVA is the predominant factor in the total costs of treatment (Figure 1). This further highlights the reality that IVR and IVA disproportionately make up the financial components of intravitreal drug treatment for CRVO. The sensitivity analysis further highlights the high cost/QALY of IVR relative to IVA and especially IVB—as high as 32 injections of IVB per year for the remaining life years could be used to equilibrate to the 2 injections of IVR per year. This study, as do most cost-analysis models, is based on the published data that assumes the affected eye to have the better acuity; if the assumption is taken that the poorer eye is the treated one, the utility lost is less impact, hence the overall cost/QALY will be less favorable for all agents.³⁴ Moreover, the ICER comparing costs of injections in a poorer-seeing eye would approach infinity as letter difference in a poorer seeing eye confers negligible additional utility. Because of the likelihood that the fellow eye will have deterioration of vision in the future as well, the actual lifetime cost/QALY is likely to be in between the two benchmarks.³¹

For other points of comparison, cost-utility from other pivotal trials for treatment of macular edema related to CRVO were modeled as outlined (Table 3). The seemingly more favorable cost/QALY for IVR in the modeled CRUISE trial compared to the LEAVO trial was predominantly because of the improved visual gains in the former, with patients having a mean BCVA of 20/25 compared to 20/50 in the latter. While it is difficult to extrapolate lifetime cost/QALY based on 6-month data from the CRUISE trial, this suggests that IVR may be feasible from a cost perspective if only short treatment course is planned and a durable visual acuity/utility level is maintained without additional expense. The modeled lifetime cost/QALY from the COPERNICUS trial appeared to be similar to those values from the LEAVO trial. The difference in the 2-year cost/QALY of IVA between COPERNICUS and SCORE2 can be predominantly attributed to the higher average number of injections in SCORE2, although the lifetime cost/QALY of IVA between the two trials were similar. Although SCORE2 on average had more injections in the IVB group during the 2 year period than in LEAVO, it had improved visual gains by approximately one line of acuity, resulting in its lower lifetime cost/QALY compared to LEAVO. Lifetime cost/QALY of IVA were similar between the two trials, which can be attributed to similar visual gains. Although these trials have demonstrated the clinical utility of each anti-VEGF agent, the inability to accurately compare the cost/QALY from one trial to another can be attributed to differences in trial protocol and inability to access precise data from investigators. As real world usage of anti-VEGF involves switching between agents, this would be expected to yield an intermediate degree of cost utility that would depend upon the timing, duration, and any differential effect with second line treatment.

Intravitreal corticosteroids treatment has also been reported to be effective for macular edema related to CRVO, although not in a comparative randomized trial.¹⁴ The FDA-approved dexamethasone intravitreal implant (Ozurdex; Allergan, Inc., Irvine, CA) has been found to be effective in phase III, randomized, controlled trials, although they lumped cases of branch retinal vein occlusion (BRVO) and CRVO.^12,13 There are no clinical trials directly comparing intravitreal anti-VEGF agents to intravitreal dexamethasone, so cost-utility compared to anti-VEGF agents is imprecise and was not modeled or calculated in the current study. Assuming all other resource utilization being equal, and that patients receive 4 dexamethasone implants over a 100 week period (~1 implant every 180 days), the cost/QALY for this time period would be $255710/QALY ($178234/QALY), but this would not account for the costs incurred due to the higher rate of induced glaucoma or cataract surgery. Although it would be difficult to extrapolate to lifetime given the unknown need of implants in perpetuity, an advantage of this treatment would be the need for less injections, meaning presumably less risk of adverse events such as endophthalmitis as well as a decreased treatment burden on the patient and fewer imaging studies. While intravitreal triamcinolone would be less costly than Ozurdex, the lack of a comparative trial precludes the ability to determine relative utility between the two treatments. Overall, corticosteroid treatment may offer better cost-utility profile than branded anti-VEGF agents, but its clinical efficacy directly compared to anti-VEGF is still to be determined.

Limitations of this study include that the “real world” usage might involve fewer injections, visits, or imaging costs, so these cost/QALY numbers might be lower. The estimation of lifetime costs (beyond the 2 year study period) and results are, perhaps, even more imprecise; these assumptions could be spurious in either direction. When treated according to investigator discretion, the 24 month outcomes of the SCORE2 trial indicated that the number of injections decreased in the second year to an average of 3.6 injections for IVB and 4.5 injections for IVA.³⁰ Likewise data from the LEAVO indicates that the number of injections from the first to the second year decreased from approximately 7–8 to 3–4.¹⁵ Thus, it would reasonable to assume that numbers of injections would be even lower beyond year 2 as has turned out to be the case with injection-based therapy of other conditions. Stability of BCVA is not established beyond the 2-year LEAVO study period, however. While all ocular adverse events and Anti-Platelet Trialists’ Collaboration-defined events were similar among all treatment groups, the rate of these events were not factored into this current study.¹⁵ Although potentially catastrophic on an individual basis, the infrequency of endophthalmitis did not impact the cost-utility calculations for each injection. Given the modest assumption of even a relatively high 0.1% rate of infectious endophthalmitis and assuming all patients with this occurrence received vitrectomy, the increased cost/QALY over the study period was negligible (increased by 0.01–0.03%).³⁵ Similarly, assuming a 0.1% (albeit high) rate of sterile intraocular inflammation would have an even smaller impact on the cost/QALY given that treatment is largely non-surgical and would be expected to accrue less costs.³⁶ According to the rates of retinal neovascularization for each agent as described in the LEAVO study and assuming that these patients were all treated with panretinal photocoagulation and received glaucoma drainage implants, the increased cost/QALY over 100 weeks would be a modest 0.1%, 0.3%, and 0.5% for IVR, IVB, and IVA respectively. A consideration beyond the scope of this study would be the impact of vision loss on the ability to work and the treatment burden (disability associated life years), even despite patients with CRVO tending to be older and less likely to be in the workforce.³³

The primary treatment for macular edema related to CRVO remains anti-VEGF agents, with multiple evidence-based clinical trial data to support the use of IVB, IVR, and IVA.^15,30 While all 3 treatments generally maintain good visual outcomes, IVB yields the most favorable cost-utility. IVA maintains acceptable cost-utility and has significantly better cost-utility compared to IVR. While ultimately clinical judgement should determine which agent to use for treatment, estimates of cost-utility provide clinicians with additional insight on their economic impact.